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Keywords = pericellular fibronectin assembly

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15 pages, 4431 KB  
Article
Alpha-Mangostin Reduces Pericellular Fibronectin on Suspended Tumor Cells and Therapeutically, but Not Prophylactically, Suppresses Distant Metastasis
by Li-Tzu Huang, Chin-Ho Kuo, Lin Tseng, Yi-Syuan Li, Li-Hsin Cheng, Chin-Yun Cheng, Shane-Rong Sheu, Wen-Tsan Chang, Chien-Chin Chen and Hung-Chi Cheng
Life 2022, 12(9), 1375; https://doi.org/10.3390/life12091375 - 2 Sep 2022
Cited by 3 | Viewed by 3239
Abstract
Major cancer deaths can be ascribed to distant metastasis to which the assembly of pericellular fibronectin (periFN) on suspended tumor cells (STCs) in the bloodstream that facilitate endothelial attachment can lead. Even though mangosteen pericarps (MP) extracts and the major component α-mangostin (α-MG) [...] Read more.
Major cancer deaths can be ascribed to distant metastasis to which the assembly of pericellular fibronectin (periFN) on suspended tumor cells (STCs) in the bloodstream that facilitate endothelial attachment can lead. Even though mangosteen pericarps (MP) extracts and the major component α-mangostin (α-MG) exhibit potent cancer chemopreventive properties, whether they can prophylactically and therapeutically be used as dietary nutraceuticals to prevent distant metastasis by suppressing periFN assembly on STCs within the circulation remains obscure. Immunofluorescence staining, MTT assays, flow cytometric assays, immunoblotting, and experimental metastasis mouse models were used to detect the effects of MP extracts or α-MG on periFN on STCs, tumor cell proliferation and apoptosis, the AKT activity, and tumor lung metastasis. The periFN assembly on STCs was significantly diminished upon treatments of STCs with either α-MG or MP extracts in a dose-dependent manner without inhibiting cell proliferation and viability due to increased AKT activity. Pretreatment of STCs with α-MG appeared to suppress tumor lung metastasis and prolong mouse survival rates. Oral gavage with MP extracts could therapeutically, but not prophylactically, prevent lung metastasis of STCs. We concluded that MP extracts or the major component α-MG may therapeutically serve as a potent anti-metastatic nutraceutical. Full article
(This article belongs to the Collection Tumor Progression, Microenvironments, and Therapeutics)
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20 pages, 42268 KB  
Article
Depleting RhoA/Stress Fiber-Organized Fibronectin Matrices on Tumor Cells Non-Autonomously Aggravates Fibroblast-Driven Tumor Cell Growth
by Li-Tzu Huang, Chen-Lung Tsai, Shin-Huei Huang, Ming-Min Chang, Wen-Tsan Chang, Li-Hsin Cheng and Hung-Chi Cheng
Int. J. Mol. Sci. 2020, 21(21), 8272; https://doi.org/10.3390/ijms21218272 - 4 Nov 2020
Cited by 3 | Viewed by 4395
Abstract
Fibronectin (FN) expressed by tumor cells has been known to be tumor suppressive but the pericellular FN (periFN) assembled on circulating tumor cells appears to evidently promote distant metastasis. Whereas the regulation of periFN assembly in suspended cells has currently been under investigation, [...] Read more.
Fibronectin (FN) expressed by tumor cells has been known to be tumor suppressive but the pericellular FN (periFN) assembled on circulating tumor cells appears to evidently promote distant metastasis. Whereas the regulation of periFN assembly in suspended cells has currently been under investigation, how it is regulated in adherent tumor cells and the role of periFN in primary tumor growth remain elusive. Techniques of RNAi, plasmid transfections, immunoblotting, fluorescence/immunohistochemistry staining, cell proliferation assays, and primary tumor growth in C57BL6 mice and Fischer 344 rats were employed in this study. We found that endogenously synthesized FN in adherent tumor cells was required for periFN assembly which was aligned by RhoA-organized actin stress fiber (SF). Depleting periFN on adherent tumor cells congruently promoted in vivo tumor growth but surprisingly did not autonomously impact on in vitro tumor cell proliferation and apoptosis, suggestive of a non-autonomous role of periFN in in vivo tumor growth. We showed that the proliferative ability of shFN-expressing tumor cells was higher than shScramble cells did in the presence of fibroblasts. Altogether, these results suggested that depriving RhoA/SF-regulated periFN matrices non-autonomously promotes fibroblast-mediated tumor cell growth. Full article
(This article belongs to the Special Issue Tumor Microenvironment and Actin Cytoskeleton in Cancer Cell Metastasis)
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37 pages, 5497 KB  
Review
Fibronectin in Cancer: Friend or Foe
by Tsung-Cheng Lin, Cheng-Han Yang, Li-Hsin Cheng, Wen-Tsan Chang, Yuh-Rong Lin and Hung-Chi Cheng
Cells 2020, 9(1), 27; https://doi.org/10.3390/cells9010027 - 20 Dec 2019
Cited by 152 | Viewed by 17746
Abstract
The role of fibronectin (FN) in tumorigenesis and malignant progression has been highly controversial. Cancerous FN plays a tumor-suppressive role, whereas it is pro-metastatic and associated with poor prognosis. Interestingly, FN matrix deposited in the tumor microenvironments (TMEs) promotes tumor progression but is [...] Read more.
The role of fibronectin (FN) in tumorigenesis and malignant progression has been highly controversial. Cancerous FN plays a tumor-suppressive role, whereas it is pro-metastatic and associated with poor prognosis. Interestingly, FN matrix deposited in the tumor microenvironments (TMEs) promotes tumor progression but is paradoxically related to a better prognosis. Here, we justify how FN impacts tumor transformation and subsequently metastatic progression. Next, we try to reconcile and rationalize the seemingly conflicting roles of FN in cancer and TMEs. Finally, we propose future perspectives for potential FN-based therapeutic strategies. Full article
(This article belongs to the Special Issue Fibronectin in Health and Diseases)
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